Interactions between hypoxia and epidermal growth factor receptor in non-small-cell-lung cancer

Tumor hypoxia has been recognized to confer resistance to anticancer therapy since the early 20th century. More recently, its fundamental role in tumorigenesis has been established. Hypoxia-inducible factor (HIF)-1 has been identified as an important transcription factor that mediates the cellular response to hypoxia, promoting both cellular survival and apoptosis under different conditions. Increased tumor cell expression of this transcription factor promotes tumor growth In vivo and is associated with a worse prognosis in patients with non-small-cell lung cancer (NSCLC) undergoing tumor resection. The epidermal growth factor receptor (EGFR) promotes tumor cell proliferation and anglogenesis and inhibits apoptosis. Epidermal growth factor receptor expression increases in a stepwise manner during tumorigenesis and is overexpressed in > 50% of NSCLC tumors. This review discusses the reciprocal relationship between tumor cell hypoxia and EGFR. Recent studies suggest that hypoxia induces expression of EGFR and its ligands. In return, EGFR might enhance the cellular response to hypoxia by increasing expression of HIF-1α, and so act as a survival factor for hypoxic cancer cells. Immunohistochemical studies on a series of resected NSCLC tumors add weight to this contention by demonstrating a close association between expression of EGFR, HIF-1α, and:1 of HIF-1's target proteins, carbonic anhydrase IX. In this article we discuss emerging treatment strategies for NSCLC that target HIF-1, HIF-1 transcriptional targets, and EGFR.

Understanding the fabric of social interactions for ridesharing through mining social networking sites

The design of applications for dynamic ridesharing or carpooling is often formulated as a matching problem of connecting people with an aligned set of transport needs within a reasonable interval of time and space. This problem formulation relegates social connections to being secondary factors. Technology assisted ridesharing applications that put the matching problem first have revealed that they suffer from being unable to address the factor of social comfort, even after adding friend features or piggybacking on social networking sites. This research aims to understand the fabric of social interactions through which ridesharing happens. We take an online observation approach in order to understand the fabric of social interactions for ridesharing that is happening in highly subscribed online groups of local residents. This understanding will help researchers to identify design challenges and opportunities to support ridesharing in local communities. This paper contributes a fundamental understanding of how social interactions and social comfort precede rideshare requests in local communities.

Carbon dioxide capture and gas separation on B80 fullerene

Exploring advanced materials for efficient capture and separation of CO2 is important for CO2 reduction and fuel purification. In this study, we have carried out first-principles density functional theory calculations to investigate CO2, N2, CH4, and H2 adsorption on the amphoteric regioselective B80 fullerene. Based on our calculations, we find that CO2 molecules form strong interactions with the basic sites of the B80 by Lewis acid–base interactions, while there are only weak bindings between the other three gases (N2, CH4, and H2) and the B80 adsorbent. The study also provides insight into the reaction mechanism of capture and separation of CO2 using the electron deficient B80 fullerene.

Delineating breast cancer cell interactions with engineered bone microenvironments

The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone-metastatic potential (T47D, SUM1315, MDA-MB-231, and the bone-seeking subline MDA-MB-231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone-specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy-based single-cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function-blocking experiments indicated that β1-integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP-2 and -9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA-MB-231BO cells in a β1-integrin-dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.

Building indicators in media assistance; four ways evaluation reports present “change”

The international aid and development community has supported programs that aim to build the capacity of media professionals or contribute to an enabling environment throughout the past 20 years. However, two decades on from the first modern media assistance programs, the sector is still struggling to identify, measure and understand the changes effected by their programs. There are questions raised as to whether it is even feasible to identify impacts on society and governance. This paper draws on some preliminary findings from a comparative thematic analysis of 47 evaluation documents of media assistance programs. The aim of this analysis is to identify trends in impact evaluation practice in the media assistance field, as well as the strengths and weaknesses of different evaluation approaches. This paper presents four types of social change claims commonly presented in reports; hypothetical changes, introduction of new opportunities, concrete examples of immediate impacts, and analysis of ongoing social and political changes. Although these types may appear as a spectrum from weak to strong, the interactions are perhaps more accurately understood using metaphors such as building blocks. This paper explores these types in more detail and suggests that a robust set of impacts-types could be useful in developing more grounded theories of change and indicators.

The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens interactions with the ocular surface and adnexa subcommittee

The report of this subcommittee concerns the impact of contact lenses (CLs) on the ocular surface, with a particular emphasis on CL discomfort (CLD). We define the ocular surface, its regional anatomy, and the physiological responses of each region to CL wear.

Going online : young children and teachers accessing knowledge through web interactions

Children accessing and using internet-connected technology is a relatively recent phenomenon, and rapidly having an impact on their experiences and activities in homes and early childhood classrooms. Technology refers to devices such as computers, smart phones and tablets - many capable of being connected to the internet - and the products, such as websites, games, and interactive stories (Plowman and McPake, 2013). These activities can be played, created, watched, listened to and read, and incorporated into traditional everyday activities. This article provides suggestions for strategies for teachers to consider when incorporating technology into early childhood education.

Mathematical investigation of the interactions between the inflammatory response and mechanical aspects of dermal wound repair

Dermal wound repair involves complex interactions between cells, cytokines and mechanics to close injuries to the skin. In particular, we investigate the contribution of fibroblasts, myofibroblasts, TGFβ, collagen and local tissue mechanics to wound repair in the human dermis. We develop a morphoelastic model where a realistic representation of tissue mechanics is key, and a fibrocontractive model that involves a reasonable approximation to the true kinetics of the important bioactive species. We use each of these descriptions to elucidate the mechanisms that generate pathologies such as hypertrophic scars, contractures and keloids. We find that for hypertrophic scar and contracture development, factors regulating the myofibroblast phenotype are critical, with heightened myofibroblast activation, reduced myofibroblast apoptosis or prolonged inflammation all predicted as mediators for scar hypertrophy and contractures. Prevention of these pathologies is predicted when myofibroblast apoptosis is induced, myofibroblast activation is blocked or TGFβ is neutralised. To investigate keloid invasion, we develop a caricature representation of the fibrocontractive model and find that TGFβ spread is the driving factor behind keloid growth. Blocking activation of TGFβ is found to cause keloid regression. Thus, we recommend myofibroblasts and TGFβ as targets for clinicians when developing intervention strategies for prevention and cure of fibrotic scars.

Understanding the implications of digital interactions on the design of public urban spaces

This study investigated the impact of digital networked social interactions on the design of public urban spaces. Urban informatics, social media, ubiquitous computing, and mobile technology offer great potential to urban planning, as tools of communication, community engagement, and placemaking. The study considers the function of public spaces as 'third places,' that is, social places that are familiar, comfortable, social and meaningful for everyday life outside the home and work. Libraries were chosen as the study's focus. The study produced findings and insights at the intersection of urban planning (place), cultural geography and urban sociology (people), and information communication technology (technology) – the triad of urban informatics.

Strong cryptography from weak secrets

Distributed-password public-key cryptography (DPwPKC) allows the members of a group of people, each one holding a small secret password only, to help a leader to perform the private operation, associated to a public-key cryptosystem. Abdalla et al. recently defined this tool [1], with a practical construction. Unfortunately, the latter applied to the ElGamal decryption only, and relied on the DDH assumption, excluding any recent pairing-based cryptosystems. In this paper, we extend their techniques to support, and exploit, pairing-based properties: we take advantage of pairing-friendly groups to obtain efficient (simulation-sound) zero-knowledge proofs, whose security relies on the Decisional Linear assumption. As a consequence, we provide efficient protocols, secure in the standard model, for ElGamal decryption as in [1], but also for Linear decryption, as well as extraction of several identity-based cryptosystems [6,4]. Furthermore, we strenghten their security model by suppressing the useless testPwd queries in the functionality.

Distributed public-key cryptography from weak secrets

We introduce the notion of distributed password-based public-key cryptography, where a virtual high-entropy private key is implicitly defined as a concatenation of low-entropy passwords held in separate locations. The users can jointly perform private-key operations by exchanging messages over an arbitrary channel, based on their respective passwords, without ever sharing their passwords or reconstituting the key. Focusing on the case of ElGamal encryption as an example, we start by formally defining ideal functionalities for distributed public-key generation and virtual private-key computation in the UC model. We then construct efficient protocols that securely realize them in either the RO model (for efficiency) or the CRS model (for elegance). We conclude by showing that our distributed protocols generalize to a broad class of “discrete-log”-based public-key cryptosystems, which notably includes identity-based encryption. This opens the door to a powerful extension of IBE with a virtual PKG made of a group of people, each one memorizing a small portion of the master key.

Organizational probes : exploring playful interactions in work environment

Playfulness, with non-intrusive elements, can be considered a useful resource for enhancing social awareness and community building within work organizations. Taking inspirations from the cultural probes approach, we developed organizational probes as a set of investigation tools that could provide useful information about employees’ everyday playful experiences within their work organizations. In an academic work environment, we applied our organizational probes over a period of three weeks. Based on the collected data we developed two design concepts for playful technologies in work environments.