Innate Lymphoid Cells are the Predominant Source of Interleukin-17A During the Early Pathogenesis of Acute Respiratory Distress Syndrome

Rationale: IL-17A is purported to help drive early pathogenesis in acute respiratory distress syndrome (ARDS) by enhancing neutrophil recruitment. Whilst IL-17A is the archetypal cytokine of T helper (Th)17 cells, it is produced by a number of lymphocytes, the source during ARDS being unknown. <br/><br/>Objectives: To identify the cellular source and the role of IL17A in the early phase of lung injury<br/><br/>Methods: Lung injury was induced in WT (C57BL/6) and IL-17 KO mice with aerosolised LPS (100 ��g) or Pseudomonas aeruginosa infection. Detailed phenotyping of the cells expressing ROR��t, the transcriptional regulator of IL-17 production, in the mouse lung at 24 hours was carried out by flow cytometry.<br/> <br/>Measurement and Main Results: A 100-fold reduction in neutrophil infiltration was observed in the lungs of the IL-17A KO compared to wild type (WT) mice. The majority of ROR��t+ cells in the mouse lung were the recently identified type 3 innate lymphoid cells (ILC3). Detailed characterisation revealed these pulmonary ILC3s (pILC3s) to be discrete from those described in the gut. The critical role of these cells was verified by inducing injury in Rag2 KO mice which lack T cells but retain ILCs. No amelioration of pathology was observed in the Rag2 KO mice.<br/><br/>Conclusions: IL-17 is rapidly produced during lung injury and significantly contributes to early immunopathogenesis. This is orchestrated largely by a distinct population of pILC3 cells. Modulation of pILC3s��� activity may potentiate early control of the inflammatory dysregulation seen in ARDS, opening up new therapeutic targets.<br/>

Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis

<p>BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in the United States. Increased level of interleukin-8 (IL-8) and CXCR2 on tumours and in the tumour microenvironment has been associated with CRC growth, progression and recurrence in patients. Here, we aimed to evaluate the effects of tissue microenvironment-encoded IL-8 and CXCR2 on colon cancer progression and metastasis.</p><p>METHODS: A novel immunodeficient, skin-specific IL-8-expressing transgenic model was generated to evaluate colon cancer growth and metastasis. Syngeneic mouse colon cancer cells were grafted in CXCR2 knockout (KO) mice to study the contribution of CXCR2 in the microenvironment to cancer growth.</p><p>RESULTS: Elevated levels of IL-8 in the serum and tumour microenvironment profoundly enhanced the growth of human and mouse colon cancer cells with increased peri-tumoural angiogenesis, and also promoted the extravasation of the cancer cells into the lung and liver. The tumour growth was inhibited in CXCR2 KO mice with significantly reduced tumour angiogenesis and increased tumour necrosis.</p><p>CONCLUSION: Increased expression of IL-8 in the tumour microenvironment enhanced colon cancer growth and metastasis. Moreover, the absence of its receptor CXCR2 in the tumour microenvironment prevented colon cancer cell growth. Together, our study demonstrates the critical roles of the tumour microenvironment-encoded IL-8/CXCR2 in colon cancer pathogenesis, validating the pathway as an important therapeutic target.</p>

Willingness to pay for potential enhancements to a low-cost cataract surgical package in rural southern China.

PURPOSE: To assess determinants of patients' willingness to pay (WTP) for potential components of a multi-tiered cataract surgical package offered by a non-governmental organization (NGO) in rural China. DESIGN: Cross-sectional study. METHODS: Demographic and clinical data were collected from 505 patients presenting for cataract screening or surgery in Yangjiang, China. Willingness to pay for potential enhancements to the current surgery package was assessed using a bidding format with random payment cards. RESULTS: Among 426 subjects (84.4%) completing interviews, the mean age was 73.9 �� 7.3 years, 67.6% were women and 73% (n = 310) would pay for at least one offering, with 33-38% WTP for each item. Among those who would pay, the mean WTP for food was US$1.68 �� 0.13, transportation US$3.24 �� 0.25, senior surgeon US$50.0 �� 3.36 and US$89.4 �� 4.19 for an imported intra-ocular lens (IOL). The estimated total recovery from these enhancements under various assumptions would be US$20-50 (compared to the current programme price of US$65). In multivariate models, WTP for the senior surgeon increased with knowledge of a person previously operated for cataract (OR = 2.13, 95% CI 1.42-3.18, p &lt; 0.001). Willingness to pay for the imported IOL increased with knowledge of a previously operated person (OR = 1.85, 95% CI 1.24-2.75, p &lt; 0.01) and decreased with age &gt;75 years (OR = 0.61, 0.40-0.93, p &lt; 0.05). CONCLUSIONS: Opportunities exist to increase cataract programme revenues through multi-tiered offerings in this setting, allowing greater subsidization of low-income patients. Personal familiarity with cataract surgery is important in determining WTP. �� 2011 The Authors. Acta Ophthalmologica �� 2011 Acta Ophthalmologica Scandinavica Foundation.

Performance Analysis of a Low Complexity Detector for MCIK-OFDM over TWDP Fading

This letter analyzes the performance of a low complexity detection scheme for a multi-carrier index keying (MCIK) with orthogonal frequency division multiplexing (OFDM) system over two-wave with diffused power (TWDP) fading channels. A closed-form expression for the average pairwise error probability (PEP) over TWDP fading channels is derived. This expression is used to analyze the performance of MCIK-OFDM in moderate, severe and extreme fading conditions. The presented results provide an insight on the performance of MCIK-OFDM for wireless communication systems that operate in enclosed metallic structures such as in-vehicular device-to-device (D2D) wireless networks.

Selective Multi-Carrier Index Keying OFDM: Error Propagation Rate with Moment Generating Function

We propose a new selective multi-carrier index keying in orthogonal frequency division multiplexing (OFDM) systems that opportunistically modulate both a small subset of sub-carriers and their indices. Particularly, we investigate the performance enhancement in two cases of error propagation sensitive and compromised deviceto-device (D2D) communications. For the performance evaluation, we focus on analyzing the error propagation probability (EPP) introducing the exact and upper bound expressions on the detection error probability, in the presence of both imperfect and perfect detection of active multi-carrier indices. The average EPP results in closedform are generalized for various fading distribution using the moment generating function, and our numerical results clearly show that the proposed approach is desirable for reliable and energy-efficient D2D applications.

A Low Complexity Detector with MRC Diversity Reception for MCIK-OFDM

Multi-carrier index keying (MCIK) is a recently developed transmission technique that exploits the sub-carrier indices as an additional degree of freedom for data transmission. This paper investigates the performance of a low complexity detection scheme with diversity reception for MCIK with orthogonal frequency division multiplexing (OFDM). For the performance evaluation, an exact and an approximate closed form expression for the pairwise error probability (PEP) of a greedy detector (GD) with maximal ratio combining (MRC) is derived. The presented results show that the performance of the GD is significantly improved when MRC diversity is employed. The proposed hybrid scheme is found to outperform maximum likelihood (ML) detection with a substantial reduction on the associated computational complexity.

Forced Displacement, Suffering and the Aesthetics of Loss

This article investigates how artists have addressed shocking experiences of displacement in different political contexts. Drawing on the notion of ���the aesthetics of loss��� (Ko��stlin, 2010), it examines and compares the different aims, desires and strategies that have shaped the histories and social lives of paintings, memorial statues, installations and other artefacts. The analysis identifies a mode of artistic engagement with the sense of a ���loss of homeland��� that has been commonly felt amongst Sudeten German expellees, namely the production and framing of visual images as markers of collective trauma. These aesthetics of loss are contrasted with the approach taken by the Dutch artist Sophie Ernst in her project entitled HOME. Working with displaced people from Pakistan, India, Palestine, Israel and Iraq, she created a mnemonic space to stimulate a more individualistic, exploratory engagement with the loss of home, which aimed, in part, to elicit interpersonal empathy. To simply oppose these two modes of aesthetic engagement, however, would ignore the ways in which artefacts are drawn into different discursive, affective and spatial formations. This article argues for the need to expose such dynamic processes of framing and reframing by focusing on the processual aspects of aestheticisation with attention to the perspective of loss.

L��nguas em Timor-Leste: que gest��o escolar do plurilinguismo?

O presente estudo tem por objetivo compreender, no contexto geopol��tico de Timor-Leste, quais as imagens, fun����es e estatutos das l��nguas que a�� circulam e, simultaneamente, percecionar de que modo a Escola gere essa pluralidade lingu��stica. Para o efeito, tivemos em conta as representa����es/imagens relativamente ��s l��nguas, ��s suas fun����es e estatutos, n��o s�� dos alunos e dos diferentes atores educativos (professores, diretores de escola e formadores do 1.�� e 2.�� ciclo), mas tamb��m aquelas que circulam em contexto social alargado, onde inclu��mos os intervenientes e os respons��veis pelas pol��ticas educativas e outros elementos da popula����o. Foi deste modo que procur��mos perceber de que forma tais representa����es se influenciam reciprocamente e se refletem na Escola. O estudo realizado foi de cariz etnogr��fico. Assim, o investigadorobservador, colocado no terreno, foi produzindo um di��rio do observador e recolhendo informa����o etnogr��fica, atrav��s da sua conviv��ncia com a sociedade timorense (escritos do quotidiano, question��rio �� pol��cia, observa����o de aula, entre outros), auscultando as ���vozes��� quer dos alunos (por meio de biografias lingu��sticas e desenhos), quer dos atores educativos (atrav��s de biografias lingu��sticas e entrevistas), quer ainda dos intervenientes nas pol��ticas educativas (com recurso a entrevistas) e de alguns jovens timorenses, recorrendo de novo ��s entrevistas. Simultaneamente, foi feita uma recolha documental, ao longo de todo o per��odo em que o estudo decorreu, que integrou fontes escritas (documentos oficiais, como sejam os documentos reguladores das pol��ticas lingu��sticas e os manuais, fontes n��o oficiais, incluindo documentos v��rios e testemunhos e fontes estat��sticas, como os Censos) e fontes n��o escritas (imagens e sons registados, estes posteriormente transcritos). Todos estes dados foram classificados em dados prim��rios e secund��rios, em fun����o da sua relev��ncia para o estudo. Para a sua an��lise socorremo-nos da an��lise de conte��do para as biografias, as entrevistas e os manuais de l��ngua portuguesa, estes no quadro de uma abordagem para a diversidade lingu��stica e cultural, de uma an��lise documental para os documentos reguladores do Sistema Educativa e outros documentos oficiais relativos ��s l��nguas e, finalmente, recorremos a uma an��lise biogr��fica (Molini��, 2011) para os desenhos realizados pelos alunos. Os resultados obtidos vieram evidenciar o multilinguismo social e escolar que se vive no pa��s, as imagens e as fun����es que as l��nguas desempenham nestes dois contextos, o escolar e o da sociedade alargada, permitindo-nos compreender que a Escola n��o �� apenas um microcosmos dentro da sociedade, mas um espa��o de encontro, por vezes de confronto, entre diversas l��nguas, culturas e identidades. Ela �� tamb��m espa��o onde as quest��es do plurilinguismo s��o mais desafiantes na medida em que as l��nguas n��o s��o apenas objeto de ensino aprendizagem, mas desempenham igualmente fun����es importantes na aquisi����o dos saberes escolares, na intera����o social e no desenvolvimento cognitivo dos alunos. Nestes contextos, ocorrem duas situa����es relevantes, uma �� o facto de a Escola ser um lugar onde os repert��rios lingu��sticos plurilingues dos alunos entram em contacto com as l��nguas de escolariza����o, o portugu��s, o t��tum e o malaio indon��sio e outra �� que saberes escolares e saberes culturais utilizam l��nguas diferentes, isto ��, os primeiros s��o veiculados em t��tum e portugu��s, eventualmente em malaio indon��sio, mas os saberes culturais s��o expressos nas l��nguas aut��ctones, amea��adas, por��m, por uma crescente expans��o do t��tum. Contudo, estas l��nguas criam tamb��m espa��os privados, identit��rios e de coes��o social dentro da grande cidade que �� D��li. S��o l��nguas ���secretas��� e ���de defesa.��� Por fim, referiremos a urg��ncia para que se tomem medidas no sentido de se criar um consenso sobre a normaliza����o do t��tum, que conduza �� sua aplica����o em contexto educativo e ao seu desenvolvimento funcional, isto ��, que leve �� planifica����o do seu estatuto. Visa-se, com este estudo, contribuir para que os atores, acima referidos, possam ��repensar�� a Escola, em Timor Leste, e, em particular, no que diz respeito �� gest��o das l��nguas que nela circulam, atrav��s de uma pol��tica lingu��stica (educativa) que beneficie o Sistema Educativo, com eventuais repercuss��es no ��mbito do curr��culo, da produ����o de materiais e da forma����o de professores. Face aos resultados obtidos, ainda que consideremos este estudo como parcelar, pelo facto de ter decorrido, sobretudo, na capital timorense, permitimo-nos sugerir a necessidade de esbater fronteiras entre o espa��o escolar e as realidades dos alunos, encontrando uma gest��o escolar deste plurilinguismo que crie um curr��culo mais integrador dos saberes lingu��sticos dos alunos.

Loss of Par3 leads to aberrant divisions and faster mitotic progression in differentiating primary murine keratinocytes

Disserta����o de Mestrado, Oncobiologia: Mecanismos Moleculares do Cancro, Faculdade de Ci��ncias e Tecnologia, Universidade do Algarve, 2015

Synaptic dysfunction in early encephalopathies : from genes to function

Tese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2015

Characterization of adenosinergic system in Rett syndrome

Tese de mestrado, Neuroci��ncias, Faculdade de Medicina, Universidade de Lisboa, 2015

Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

A study on dynamic state information (DSI) around users for safe urban life

To select each node by devices and by contexts in urban computing, users have to put their plan information and their requests into a computing environment (ex. PDA, Smart Devices, Laptops, etc.) in advance and they will try to keep the optimized states between users and the computing environment. However, because of bad contexts, users may get the wrong decision, so, one of the users��� demands may be requesting the good server which has higher security. To take this issue, we define the structure of Dynamic State Information (DSI) which takes a process about security including the relevant factors in sending/receiving contexts, which select the best during user movement with server quality and security states from DSI. Finally, whenever some information changes, users and devices get the notices including security factors, then an automatic reaction can be possible; therefore all users can safely use all devices in urban computing.

Contexts-management strategy in considering the security in urban computing based on urban design

Urban Computing (UrC) provides users with the situation-proper information by considering context of users, devices, and social and physical environment in urban life. With social network services, UrC makes it possible for people with common interests to organize a virtual-society through exchange of context information among them. In these cases, people and personal devices are vulnerable to fake and misleading context information which is transferred from unauthorized and unauthenticated servers by attackers. So called smart devices which run automatically on some context events are more vulnerable if they are not prepared for attacks. In this paper, we illustrate some UrC service scenarios, and show important context information, possible threats, protection method, and secure context management for people.