Streptococcal collagen-like surface protein 1 promotes adhesion to the respiratory epithelial cell

BACKGROUND: Collagen-like surface proteins Scl1 and Scl2 on Streptococcus pyogenes contain contiguous Gly-X-X triplet amino acid motifs, the characteristic structure of human collagen. Although the potential role of Scl1 in adhesion has been studied, the conclusions may be affected by the use of different S. pyogenes strains and their carriages of various adhesins. To explore the bona fide nature of Scl1 in adherence to human epithelial cells without the potential interference of other streptococcal surface factors, we constructed a scl1 isogenic mutant from the Scl2-defective S. pyogenes strain and a Scl1-expressed Escherichia coli. RESULTS: Loss of Scl1 in a Scl2-defective S. pyogenes strain dramatically decreased the adhesion of bacteria to HEp-2 human epithelial cells. Expression of Scl1 on the surface of the heterologous bacteria E. coli significantly increased adhesion to HEp-2. The increase in adhesion was nullified when Scl1-expressed E. coli was pre-incubated with proteases or antibodies against recombinant Scl1 (rScl1) protein. Treatment of HEp-2 cells with rScl protein or pronase drastically reduced the binding capability of Scl1-expressed E. coli. These findings suggest that the adhesion is mediated through Scl1 on bacterial surface and protein receptor(s) on epithelial cells. Further blocking of potential integrins revealed significant contributions of α2 and β1 integrins in Scl1-mediated binding to epithelial cells. CONCLUSIONS: Together, these results underscore the importance of Scl1 in the virulence of S. pyogenes and implicate Scl1 as an adhesin during pathogenesis of streptococcal infection

Look, the World is Watching How We Treat Migrants! The Making of the Anti-Trafficking Legislation during the Ma Administration

Employing the spiral model, this research analyses how anti-human trafficking legislation was promulgated during the Ma Ying-jeou (Ma Yingjiu) presidency. This research found that the gov- ernment of Taiwan was just as accountable for the violation of mi- grants’ human rights as the exploitive placement agencies and abusive employers. This research argues that, given its reliance on the United States for political and security support, Taiwan has made great ef- forts to improve its human rights records and meet US standards for protecting human rights. The reform was a result of multilevel inputs, including US pressure and collaboration between transnational and domestic advocacy groups. A major contribution of this research is to challenge the belief that human rights protection is intrinsic to dem- ocracy. In the same light, this research also cautions against Taiwan’s subscription to US norms since the reform was achieved at the cost of stereotyping trafficking victimhood, legitimising state surveillance, and further marginalising sex workers

The Affinity of Elongated Membrane-Tethered Ligands Determines Potency of T Cell Receptor Triggering

T lymphocytes are important mediators of adoptive immunity but the mechanism of T cell receptor (TCR) triggering remains uncertain. The interspatial distance between engaged T cells and antigen-presenting cells (APCs) is believed to be important for topological rearrangement of membrane tyrosine phosphatases and initiation of TCR signaling. We investigated the relationship between ligand topology and affinity by generating a series of artificial APCs that express membrane-tethered anti-CD3 scFv with different affinities (OKT3, BC3, and 2C11) in addition to recombinant class I and II pMHC molecules. The dimensions of membrane-tethered anti-CD3 and pMHC molecules were progressively increased by insertion of different extracellular domains. In agreement with previous studies, elongation of pMHC molecules or low-affinity anti-CD3 scFv caused progressive loss of T cell activation. However, elongation of high-affinity ligands (BC3 and OKT3 scFv) did not abolish TCR phosphorylation and T cell activation. Mutation of key amino acids in OKT3 to reduce binding affinity to CD3 resulted in restoration of topological dependence on T cell activation. Our results show that high-affinity TCR ligands can effectively induce TCR triggering even at large interspatial distances between T cells and APCs

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 1

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Has Digital Opportunity Center initiated the development of remote area ?- the case study of gluban tribe in NanTou

本文以南投縣仁愛鄉清流部落為深度報導對象，以數位機會中心的角度，觀察政府推行縮減城鄉數位落差的政策落實到在地的情形為何。報導者主要運用深度訪談法，搭配田野觀察法蒐集報導素材。報導發現，影響數位機會中心實際運作情況的原因共可分為六個面向，包括：營運者與輔導團隊、當地人口結構、當地經濟問題、其他民間組織、部落既有優勢，以及經營者對數位機會中心的看法。此外，本文也發現，數位機會中心雖背負著縮減城鄉數位落差、帶動社區發展的政府期待，但對照到部落的在地需求及想像，則是另一種落差。本文的貢獻在於累積本土縮減城鄉數位落差政策的實際經驗，並提出反思及建議，期能作為政府未來規劃相關政策的參考。Alan Gluban, a tribe in Renai Township, Nantou County, at the central part of Taiwan, is the subject of this in-depth report. From the viewpoint of The Digital Opportunity Center (DOC), this article provides a glimpse of the differences between the government policy and the local executions of digital divide. In-depth interviews and field observation are used as the research methods to collect data. The report found that six factors influenced the management of DOC in different angles: the manager of DOC and the guidance of DOC, local population structure, local economy, local organizations, historical advantages and the way the manager regards DOC. Additionally, the government depends on DOC to curtail the digital divide between the rural and urban areas in Taiwan, and also expects DOC to enhance the community development through its routine tasks. Moreover, this article also reveals that DOC’s execution leads to another kind of divide: the reality of local requirements and visions are not the same as what government imagined. The article’s contribution lies in blending the insight of DOC and the local experiences of the trial of reducing digital divide, which enables the author to give out suggestions and self-examination methods as the government’s references in drawing up related policies in the future.口試委員審定書 i辭 ii文摘要 iii文摘要 iv一章 前言 1一節 研究緣起 2二節 清流部落 10三節 研究問題 14四節 研究架構 17二章 文獻回顧 19一節 數位落差 20二節 社區發展 28三章 研究方法與報導對象 41一節 研究方法 42二節 報導對象─清流部落 45四章 深度報導 50一節 前言 51二節 和你想像不同的原鄉部落─ALAN-GLUBAN 52三節 褒貶參半的社區發展協會 55四節 數位機會中心資源使用情形 60五節 不同位置的人看「數位機會中心」資源 74六節 數位機會中心與社區發展 78五章 結論 86一節 報導發現 87二節 報導限制與建議 91三節 報導後記 92考書目 9

A RRAM Integrated 4T SRAM with Self-Inhibit Resistive Switching Load by Pure CMOS Logic Process

Abstract This paper reports a novel full logic compatible 4T2R non-volatile static random access memory (nv-SRAM) featuring its self-inhibit data storing mechanism for in low-power/high-speed SRAM application. With compact cell area and full logic compatibility, this new nv-SRAM incorporates two STI-ReRAMs embedded inside the 4T SRAM. Data can be read/write through a cross-couple volatile structure for maintaining fast accessing speed. Data can be non-volatilely stored in new SRAM cell through a unique self-inhibit operation onto the resistive random access memory (RRAM) load, achieving zero static power during data hold

The CCL2/CCR2 axis enhances vascular cell adhesion molecule-1 expression in human synovial fibroblasts.

Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of osteoarthritis (OA). Here, we investigated the intracellular signaling pathways involved in CCL2-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human OA synovial fibroblasts (OASFs).Stimulation of OASFs with CCL2 induced VCAM-1 expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor (RS102895), PKCδ inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 increased PKCδ and p38MAPK activation. Treatment of OASFs with CCL2 also increased the c-Jun phosphorylation and c-Jun binding to the AP-1 element on the VCAM-1 promoter. Moreover, CCL2-mediated CCR2, PKCδ, p38MAPK, and AP-1 pathway promoted the adhesion of monocytes to the OASFs monolayer.Our results suggest that CCL2 increases VCAM-1 expression in human OASFs via the CCR2, PKCδ, p38MAPK, c-Jun, and AP-1 signaling pathway. The CCL2-induced VCAM-1 expression promoted monocytes adhesion to human OASFs

The Impact of the Hazard Correlation between Risk Factors and Diabetes

This study examined the occurrence of diabetes and sustainable risk factors in residents aged 30 and above of a community in Taoyuan County, Taiwan. The main purpose of this research was to explore the correlations between related variables and the occurrence of diabetes. The demographic variables, health exam variables, healthy behavior variables, and environmental variables had obvious impacts on the risk of diabetes. As age increased, the risk of developing the disease also increased; higher educational levels lowered risk, while unemployment raised it. Also, analysis of the health exam variables showed that abnormal BMIs, waist-hip ratios, and body fat percentages had significant impacts on individuals’ risk of diabetes. Moreover, it was found that smoking affected the risk of having diabetes: smokers, particularly male smokers, had a relatively higher risk of developing the disease. Lastly, the results showed that exposure to second-hand smoke did not have a significant effect on the diabetes proportion in the male population. However, a significantly higher proportion of females who had been exposed to second-hand smoke had diabetes

Hazard Prevention Regarding Occupational Accidents Involving Blue-Collar Foreign Workers: A Perspective of Taiwanese Manpower Agencies

Since 1989, blue-collar foreign workers have been permitted to work in Taiwanese industries. Most blue-collar foreign workers apply for jobs in Taiwan through blue-collar foreign workers’ agencies. Because blue-collar foreign workers are not familiar with the language and culture in Taiwan, in occupational accident education and hazard prevention, the agencies play an important role in the coordination and translation between employees and blue-collar foreign workers. The purpose of this study is to establish the agencies’ role in the occupational accidents education and hazard prevention for blue-collar foreign workers in Taiwan. This study uses a qualitative method—grounded theory—to collect, code, and analyze the data in order to understand the agencies’ role in occupational accident education and hazard prevention for blue-collar foreign workers in Taiwan. The results show that the duty of agencies in occupational accident education and hazard prevention includes selecting appropriate blue-collar foreign workers, communicating between employees and blue-collar foreign workers, collecting occupational safety and health information, assisting in the training of occupational safety and health, and helping blue-collar foreign workers adapt to their lives in Taiwan. Finally, this study suggests seven important points and discusses the implementation process necessary to improve governmental policies. The government and employees should pay attention to the education/training of occupational safety and health for blue-collar foreign workers to eliminate unsafe behavior in order to protect the lives of blue-collar foreign workers