POTs: Protective Optimization Technologies

Algorithmic fairness aims to address the economic, moral, social, and political impact that digital systems have on populations through solutions that can be applied by service providers. Fairness frameworks do so, in part, by mapping these problems to a narrow definition and assuming the service providers can be trusted to deploy countermeasures. Not surprisingly, these decisions limit fairness frameworks' ability to capture a variety of harms caused by systems. We characterize fairness limitations using concepts from requirements engineering and from social sciences. We show that the focus on algorithms' inputs and outputs misses harms that arise from systems interacting with the world; that the focus on bias and discrimination omits broader harms on populations and their environments; and that relying on service providers excludes scenarios where they are not cooperative or intentionally adversarial. We propose Protective Optimization Technologies (POTs). POTs provide means for affected parties to address the negative impacts of systems in the environment, expanding avenues for political contestation. POTs intervene from outside the system, do not require service providers to cooperate, and can serve to correct, shift, or expose harms that systems impose on populations and their environments. We illustrate the potential and limitations of POTs in two case studies: countering road congestion caused by traffic-beating applications, and recalibrating credit scoring for loan applicants.Comment: Appears in Conference on Fairness, Accountability, and Transparency (FAT* 2020). Bogdan Kulynych and Rebekah Overdorf contributed equally to this work. Version v1/v2 by Seda G\"urses, Rebekah Overdorf, and Ero Balsa was presented at HotPETS 2018 and at PiMLAI 201

Chemical Genetics Reveals an RGS/G-Protein Role in the Action of a Compound

We report here on a chemical genetic screen designed to address the mechanism of action of a small molecule. Small molecules that were active in models of urinary incontinence were tested on the nematode Caenorhabditis elegans, and the resulting phenotypes were used as readouts in a genetic screen to identify possible molecular targets. The mutations giving resistance to compound were found to affect members of the RGS protein/G-protein complex. Studies in mammalian systems confirmed that the small molecules inhibit muscarinic G-protein coupled receptor (GPCR) signaling involving G-αq (G-protein alpha subunit). Our studies suggest that the small molecules act at the level of the RGS/G-αq signaling complex, and define new mutations in both RGS and G-αq, including a unique hypo-adapation allele of G-αq. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation

Discovery of several thousand highly diverse circular DNA viruses.

Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over 70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere

Discovery of several thousand highly diverse circular DNA viruses.

Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over 70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere

Discovery of several thousand highly diverse circular DNA viruses

Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over 70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere

Getting By the Occupation: How Violence became Normal during the Second Palestinian Intifada

The second Palestinian intifada against Israeli occupation, which began in September 2000, saw Palestinian areas repeatedly invaded and shelled by Israeli forces. A long history of war and targeted cities is told along the thoroughfares of Palestinian towns; memories of past battles and defeats inscribed in street signs recall massacres in places like Tel Al-Za'atar and Deir Yasin. But recent events were more important than any official marker and formed the most relevant base by which Palestinians organized their lives. Commemorative cultural production and basic acts of physically getting around that became central to the spatial and social practices by which reorientation and adaptation to violence occurred in the occupied Palestinian territories. This article analyzes the spaciotemporal, embodied, and symbolic aspects of the experience of violence, and the political significance of cultural practices whereby violence is routinized. Such an approach provides a lens onto the power of violence in Israel's colonial project in the occupied territories that neither necessitates an assumption that violence is all determining of Palestinian experience, nor a championing of every act of Palestinian survival as heroic resistance. Memorialization that occurs in storytelling, in visual culture, in the naming of places and moving through spaces is one way in which this happens. The concept of “getting by” captures the many spatial and commemorative forms by which Palestinians manage everyday survival. The kind of agency that is entailed in practices whereby people manage, get by, adapt, and the social significance of getting used to it may be somewhat nebulous and unobtrusive as it develops in the shadow of spectacular battles and bloodshed. I demonstrate that this routinization of violence in and of itself, the fact of getting by, just existing in an everyday way, is socially and politically significant in Palestine

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection

Effect of BMS-192364 in Combination with Other Modulators of Calcium Signaling

<div><p>The graphs display fluorescence intensity measurements for HEK293 cells preloaded with Fluo-4 then stimulated with the muscarinic GPCR agonist carbachol at 100 μM. Five baseline fluorescence measurements were taken prior to the injection of carbachol. Where indicated, BMS-195270 or BMS-192364 (100 μM) were added 15 min prior to the carbachol stimulation. The timing of carbachol addition is indicated by a black arrowhead.</p><p>(A) Where indicated, cells were pre-incubated for 15 min with the calcium channel blocker niguldipine (100 μM).</p><p>(B) Where indicated, cells were pre-incubated for 24 h with the G-protein antagonist pertussis toxin (150 ng/ml).</p><p>(C) The treated cells are overexpressing the G-αq mutant allele G188S, which is known to be insensitive to RGS GAP activity.</p></div