The nuanced negative: Meanings of a negative diagnostic result in clinical exome sequencing

Genomic sequencing technology is moving rapidly from the research setting into clinical medicine but significant technological and interpretive challenges remain. Whole exome sequencing (WES) in its recent clinical application provides a genetic diagnosis in about 25% of cases (Berg 2014). While this diagnostic yield is substantial, it also indicates that in a majority of cases, patients are receiving negative results (i.e., no explanatory genetic variant found) from this technology. There are a number of uncertainties regarding the meaning of a negative result in the current context of WES. A negative result may be due to current technological limitations that hinder detection of disease-causing variants or to gaps in the knowledge base that prohibit accurate interpretation of their pathogenicity; or it may indicate that there is not a genetic etiology for the disorder. In this paper we examine the uncertainties and nuances of the negative result from genome sequencing and how both clinicians and patients make meaning of it as revealed in ethnographic observations of the clinic session where results are returned, and in interviews with patients. We find that clinicians and patients construct the meaning of a negative result in ways that are uncertain, contingent, and multivalent; but invested with optimism, promise, and potentiality

Conflicted Conceptions: An Ethnography of Assisted Reproduction Practices in Argentina

In this ethnography, I focus on the community of reproductive medicine professionals in Argentina to examine how assisted reproductive technologies (ART) are transformed according to local conditions of practice, as well as how they are transformative of the societies they newly inhabit. Based on three continuous years of ethnographic, interview and archival research conducted primarily in Buenos Aires, my findings reveal that the production of ART in a given place is not a culturally-neutral process, but rather involves local forms of science, medicine, modernity, morality and choice. In chapter one, I give a contextual history of how ART began in Argentina, and locate today's Argentine infertility specialists within a transnational network of training, scientific prestige, innovation and competition. In chapter two, I examine the specificities of the local production of ART in Buenos Aires, which include a series of moral positions on family, motherhood, and the role of the Catholic Church in medical practice, as well as creative maneuverings around legal, economic and political constraints. In chapter three, I analyze the practice of gamete donation in Argentina, in which beliefs about genetic inheritance, options for family making, and the market-side of reproductive medicine all intersect. In chapter four, I focus on the problematic of the morally and legally ambiguous embryo, and examine two techniques in particular, embryo cryopreservation and preimplantation genetic diagnosis (PGD), to illustrate how medical and scientific protocols are translated to fit local conditions of practice. Throughout these chapters I argue that the production of these medical technologies are shifting deeply rooted beliefs about the sanctity of human life and the role of technology in manipulating that life. I conclude that currently in Argentina the reproductive medicine professionals who provide ART to the public are society's moral guardians, diagnosing the healthy body and family, defining when personhood begins, and dictating what protections are due human life. In the last instance, this cultural analysis is revealing not only of assisted reproduction practices in Argentina, but also circulates back to inform the production of ART as a global medical technology

Structural revelations of photosynthesis' membrane protein complexes

Photosynthetic organisms appeared early in evolution and their photosynthetic apparatus has evolved along. The first bacteria carried out only anoxygenic photosynthesis catalyzed by one type of reaction center, type I or II, which somehow came together in cyanobacteria, and evolved into photosystems I and II. This was an evolutionary step that enabled cyanobacteria to carry out oxygenic photosynthesis. The photosystems have the unique capacity to perform and fix energy in a process where water splitting and oxygen evolution takes place, providing planet Earth with an essential molecule for development of life, i.e. Oxygen. Throughout evolution, primordial organisms became more complex upon colonizing diverse environments resulting into the current day sophisticated systems. Nevertheless, the photosystems have preserved their vital mechanisms of sunlight conversion with PSI at almost 100% efficiency, and PSII’s unique water splitting property. Important about photosynthesis systems are the high-energy conversion efficiency and oxygen evolution besides hydrogen generation by some organisms like cyanobacteria. These features are precious global demands for efficient sun utilizing devices, environmental concerns and current economics of alternative energy source to fossil fuel depletion. The diversity of the photosynthesis proteins due to evolution upon adaptation and exploitability is intriguing for researchers from all fields of science to understand aspects of structural diversity, function and dynamics. This work is highly complementary and has been carried out in multidisciplinary collaborations to get more impact for understanding the photosynthesis systems that evolved early or later. The results of which can be integrated into applied technology.

The exon-intron structure and chromosomal localization of the mouse macrophage mannose receptor gene Mrc1: identification of a Ricin-like domain at the N-terminus of the receptor.

The macrophage mannose receptor is a transmembrane protein that is expressed on the surface of mature macrophages. The ectodomain of the receptor contains multiple domains, eight of which belong to the calcium-dependent C-type lectin family. The mannose receptor binds to carbohydrate polymers that have a high content of mannose. This property allows this protein to function as a phagocytic receptor that participates in first-line host defense against invading microorganisms. In this paper we describe the intron-exon structure of the mouse macrophage mannose receptor gene which was found to span at least 70 kilobases. We also report the localization of this gene, termed Mrc1, to mouse Chromosome 2. Like its human counterpart, Mrc1 contains 30 exons and 29 introns. A protein module that resembles a subdomain of the B chain of the plant lectin Ricin has been found within the N-terminal cysteine-rich domain of the mannose receptor

UbiKit: Learning to Prototype for Tangible and Ubiquitous Computing

As more and more ubiquitous computing (ubicomp) technologies pervade our daily lives, it is becoming increasingly important to train interaction design students to create these technologies. However, teaching students to design ubicomp technologies can be challenging, because creating a prototype, which people can use and students can learn from, usually requires a long setup and development phase. While there are some prototyping kits available, such as Arduino or the Raspberry Pi, they often require relatively steep learning curves before anything sophisticated can be prototyped. For this reason, we created UbiKit, a quick-to-setup, reusable, and affordable toolkit for the rapid design of ubicomp technologies that enable people to co-explore different scenarios and focus on the users. We piloted UbiKit in a Master-level course on ubicomp related topics and reflect on its potential to help streamline the prototyping and overall learning process for students being trained in our research area