Instruments of Commerce and Knowledge: Probe Microscopy, 1980-2000

Longstanding debates about the role of the university in national culture and the global economy have entered a new phase in the past decade in most industrialized, and several industrializing, countries. One important focus of this debate is corporate involvement in academic scientific research. Proponents of the academic capitalism say that corporate involvement makes the university leaner, more agile, better able to respond to the needs of the day. Critics say that corporate involvement leaves society without the independent, critical voices traditionally lodged in universities. I argue that a science and technology studies perspective, using case studies of research communities, can push this debate in directions envisioned by neither proponents nor critics. I use the development and commercialization of the scanning tunneling microscope and the atomic force microscope as an example of how research communities continually redraw the line between corporate and academic institutions.

The Squares

When ungroovy scientists did groovy science: how non-activist scientists and engineers adapted their work to a rapidly changing social and political landscape. In The Squares, Cyrus Mody shows how, between the late 1960s and the early 1980s, some scientists and engineers who did not consider themselves activists, New Leftists, or members of the counterculture accommodated their work to the rapidly changing social and political landscape of the time. These “square scientists,” Mody shows, began to do many of the things that the counterculture urged: turn away from military-industrial funding, become more interdisciplinary, and focus their research on solving problems of civil society. During the period Mody calls “the long 1970s,” ungroovy scientists were doing groovy science. Mody offers a series of case studies of some of these collective efforts by non-activist scientists to use their technical knowledge for the good of society. He considers the region around Santa Barbara and the interplay of public universities, think tanks, established firms, new companies, philanthropies, and social movement organizations. He looks at Stanford University's transition from Cold War science to commercialized technoscience; NASA's search for a post-Apollo mission; the unsuccessful foray into solar energy by Nobel laureate Jack Kilby; the “civilianization” of the US semiconductor industry; and systems engineer Arthur D. Hall's ill-fated promotion of automated agriculture

PD‐1 inhibition in congenital pigment synthesizing metastatic melanoma

A newborn female child was born with a congenital pigment synthesizing melanoma of the scalp. Further workup revealed metastatic disease within the liver, lungs, and left tibia. Whole exome sequencing was performed on multiple samples that revealed one somatic mutation, lysine methyltransferase 2C (KMT2C), at low allelic frequency but no v‐Raf murine sarcoma viral oncogene homolog B (BRAF), NF‐1 mutation. Programmed death ligand 1 was moderately expressed. Treatment was initiated with the programmed cell death protein 1 inhibitor nivolumab. The patient tolerated this treatment well with minimal toxicity. She is now over a year out from initial diagnosis, continuing on nivolumab, with stable disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139985/1/pbc26702.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139985/2/pbc26702_am.pd

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents.

Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets

Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1B.

Protein tyrosine phosphatase 1B (PTP1B) regulates various signalling pathways including insulin, leptin, IGF-1 and growth hormone (GH) signalling. Transmission of the GH signal depends on Janus kinase 2 (JAK2), which is how PTP1B is thought to modulate GH signalling in the liver, based on studies utilising global PTP1B knockout mice (Ptp1b(-/-)). Here, we investigated the liver-specific role of PTP1B in GH signalling, using liver-specific Ptp1b(-/-) mice (alb-crePtp1b(-/-)), under physiological (chow) or insulin resistant (high-fat diet [HFD]) feeding conditions. Body weight and adiposity were comparable between female alb-crePtp1b(-/-) and Ptp1b(fl/fl) control mice. On chow diet, under 48-hour fasting GH-resistant conditions, GH stimulation in vivo led to a robust stimulation of the JAK-STAT signalling pathway. Alb-crePtp1b(-/-) mice exhibited significantly higher GH-induced JAK2 phosphorylation and SOCS3 gene expression post-GH stimulation. However, STAT3, STAT5 and ERK1/2 phosphorylation and SOCS2 gene expression were similar between groups. Interestingly, GH-induced mTOR phosphorylation was significantly higher in alb-crePtp1b(-/-) mice 5-min post-GH stimulation compared to controls, revealing this part of the pathway under direct control of PTP1B. Under ad lib HFD-fed conditions, GH-induced STAT5 phosphorylation significantly increased in alb-crePtp1b(-/-) mice only, with no alterations in the controls. Overall, our data demonstrate that liver-specific PTP1B deletion leads to significant alterations in GH signalling with increased JAK2, STAT5 and mTOR phosphorylation and SOCS3 gene expression

Entanglement of Imaging and Imagining of Nanotechnology

Images, ranging from visualizations of the nanoscale to future visions, abound within and beyond the world of nanotechnology. Rather than the contrast between imaging, i.e. creating images that are understood as offering a view on what is out there, and imagining, i.e. creating images offering impressions of how the nanoscale could look like and images presenting visions of worlds that might be realized, it is the entanglement between imaging and imagining which is the key to understanding what images do. Three main arenas of entanglement of imag(in)ing and the tensions involved are discussed: production practices and use of visualizations of the nanoscale; imag(in)ing the future and the present; and entanglements of nanoscience and art. In these three arenas one sees struggles about which images might stand for nanotechnology, but also some stabilization of the entanglement of imag(in)ing, for example in established rules in the practices of visualizing the nanoscale. Three images have become iconic, through the combination of their wide reception and further circulation. All three, the IBM logo, the Foresight Institute’s Nanogear image, and the so-called Nanolouse, depict actual or imagined technoscientific objects and are thus seen as representing technoscientific achievements – while marking out territory

Beyond Implications and Applications: the Story of ‘Safety by Design’

Using long-term anthropological observations at the Center for Biological and Environmental Nanotechnology in Houston, Texas, the article demonstrates in detail the creation of new objects, new venues and new modes of veridiction which have reoriented the disciplines of materials chemistry and nanotoxicology. Beginning with the confusion surrounding the meaning of ‘implications’ and ‘applications’ the article explores the creation of new venues (CBEN and its offshoot the International Council on Nanotechnology); it then demonstrates how the demands for a responsible, safe or ethical science were translated into new research and experiment in and through these venues. Finally it shows how ‘safety by design’ emerged as a way to go beyond implications and applications, even as it introduced a whole new array of controversies concerning its viability, validity and legitimacy

Mathematically aggregating experts' predictions of possible futures

Structured protocols offer a transparent and systematic way to elicit and combine/aggregate, probabilistic predictions from multiple experts. These judgements can be aggregated behaviourally or mathematically to derive a final group prediction. Mathematical rules (e.g., weighted linear combinations of judgments) provide an objective approach to aggregation. The quality of this aggregation can be defined in terms of accuracy, calibration and informativeness. These measures can be used to compare different aggregation approaches and help decide on which aggregation produces the “best” final prediction. When experts’ performance can be scored on similar questions ahead of time, these scores can be translated into performance-based weights, and a performance-based weighted aggregation can then be used. When this is not possible though, several other aggregation methods, informed by measurable proxies for good performance, can be formulated and compared. Here, we develop a suite of aggregation methods, informed by previous experience and the available literature. We differentially weight our experts’ estimates by measures of reasoning, engagement, openness to changing their mind, informativeness, prior knowledge, and extremity, asymmetry or granularity of estimates. Next, we investigate the relative performance of these aggregation methods using three datasets. The main goal of this research is to explore how measures of knowledge and behaviour of individuals can be leveraged to produce a better performing combined group judgment. Although the accuracy, calibration, and informativeness of the majority of methods are very similar, a couple of the aggregation methods consistently distinguish themselves as among the best or worst. Moreover, the majority of methods outperform the usual benchmarks provided by the simple average or the median of estimates

Smoking and health-related quality of life in English general population: Implications for economic evaluations

Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status