Negotiating Agency and Control: Theorizing Human-Machine Communication from a Structurational Perspective

Intelligent technologies have the potential to transform organizations and organizing processes. In particular, they are unique from prior organizational technologies in that they reposition technology as agent rather than a tool or object of use. Scholars studying human-machine communication (HMC) have begun to theorize the dual role played by human and machine agency, but they have focused primarily on the individual level. Drawing on Structuration Theory (Giddens, 1984), we propose a theoretical framework to explain agency in HMC as a process involving the negotiation of control between human and machine agents. This article contributes to HMC scholarship by offering a framework and research agenda to guide future theory-building and research on the use of intelligent technologies in organizational contexts

SN2012ab: A Peculiar Type IIn Supernova with Aspherical Circumstellar Material

We present photometry, spectra, and spectropolarimetry of supernova (SN) 2012ab, mostly obtained over the course of $\sim 300$ days after discovery. SN 2012ab was a Type IIn (SN IIn) event discovered near the nucleus of spiral galaxy 2MASXJ12224762+0536247. While its light curve resembles that of SN 1998S, its spectral evolution does not. We see indications of CSM interaction in the strong intermediate-width emission features, the high luminosity (peak at absolute magnitude $M=-19.5$), and the lack of broad absorption features in the spectrum. The H$\alpha$ emission undergoes a peculiar transition. At early times it shows a broad blue emission wing out to $-14{,}000$ km $\mathrm{s^{-1}}$ and a truncated red wing. Then at late times ($>$ 100$\,$days) it shows a truncated blue wing and a very broad red emission wing out to roughly $+20{,}000$ km $\mathrm{s^{-1}}$. This late-time broad red wing probably arises in the reverse shock. Spectra also show an asymmetric intermediate-width H$\alpha$ component with stronger emission on the red side at late times. The evolution of the asymmetric profiles requires a density structure in the distant CSM that is highly aspherical. Our spectropolarimetric data also suggest asphericity with a strong continuum polarization of $\sim 1-3$% and depolarization in the H$\alpha$ line, indicating asphericity in the CSM at a level comparable to that in other SNe IIn. We estimate a mass-loss rate of $\dot{M} = 0.050\, {\rm M}_{\odot}\,\mathrm{yr^{-1}}$ for $v_{\rm pre} = 100$$\,$km$\,$$\mathrm{s^{-1}}$ extending back at least 75$\,$yr prior to the SN. The strong departure from axisymmetry in the CSM of SN 2012ab may suggest that the progenitor was an eccentric binary system undergoing eruptive mass loss.Comment: 18 pages, 12 figure

Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway

While treatments that induce DNA damage are commonly used as anti-cancer therapies, the mechanisms through which DNA damage produces a therapeutic response are incompletely understood. Here we have tested whether medulloblastomas must be competent for apoptosis to be sensitive to radiation therapy. Whether apoptosis is required for radiation sensitivity has been controversial. Medulloblastoma, the most common malignant brain tumor in children, is a biologically heterogeneous set of tumors typically sensitive to radiation and chemotherapy; 80% of medulloblastoma patients survive long-term after treatment. We used functional genetic studies to determine if the intrinsic apoptotic pathway is required for radiation to produce a therapeutic response in mice with primary, Shh-driven medulloblastoma. We found that cranial radiation extended the survival of medulloblastoma-bearing mice and induced widespread apoptosis. Expression analysis and conditional deletion studies showed that p53 was the predominant transcriptional regulator activated by radiation and was strictly required for treatment response. Deletion of Bax, which blocked apoptosis downstream of p53, was sufficient to render tumors radiation resistant. In apoptosis-incompetent, Bax-deleted tumors, radiation activated p53-dependent transcription without provoking cell death and caused two discrete populations to emerge. Most radiated tumor cells underwent terminal differentiation. Perivascular cells, however, quickly resumed proliferation despite p53 activation, behaved as stem cells, and rapidly drove recurrence. These data show that radiation must induce apoptosis in tumor stem cells to be effective. Mutations that disable the intrinsic apoptotic pathways are sufficient to impart radiation resistance. We suggest that medulloblastomas are typically sensitive to DNA-damaging therapies because they retain apoptosis competence

Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda.

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children

Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection

<p>Abstract</p> <p>Background</p> <p>Elite non-progressors (plasma viral load <50 copies/ml while antiretroviral naive) constitute a tiny fraction of HIV-infected individuals. After 12 years follow-up of a cohort of 13 long-term non-progressors (LTNP) identified from 135 individuals with transfusion-acquired HIV infection, 5 remained LTNP after 23 to 26 years infection, but only 3 retained elite LTNP status. We examined the mechanisms that differentiated delayed progressors from LTNP in this cohort.</p> <p>Results</p> <p>A survival advantage was conferred on 12 of 13 subjects, who had at least one host genetic factor (HLA, chemokine receptor or TLR polymorphisms) or viral attenuating factor (defective <it>nef</it>) associated with slow progression. However, antiviral immune responses differentiated the course of disease into and beyond the second decade of infection. A stable p24-specific proliferative response was associated with control of viraemia and retention of non-progressor status, but this p24 response was absent or declined in viraemic subjects. Strong Gag-dominant cytotoxic T lymphocyte (CTL) responses were identified in most LTNP, or Pol dominant-CTL in those with <it>nef</it>-defective HIV infection. CTL were associated with control of viraemia when combined with p24 proliferative responses. However, CTL did not prevent late disease progression. Individuals with sustained viral suppression had CTL recognising numerous Gag epitopes, while strong but restricted responses to one or two immunodominant epitopes was effective for some time, but failed to contain viraemia over the course of this study. Viral escape mutants at a HLA B27-restricted Gag-p24 epitope were detected in only 1 of 3 individuals, whereas declining or negative p24 proliferative responses occurred in all 3 concurrent with an increase in viraemia.</p> <p>Conclusion</p> <p>Detectable viraemia at study entry was predictive of loss of LTNP status and/or disease progression in 6 of 8, and differentiated slow progressors from elite LTNP who retained potent virological control. Sustained immunological suppression of viraemia was independently associated with preserved p24 proliferative responses, regardless of the strength and breadth of the CTL response. A decline in this protective p24 response preceded or correlated with loss of non-progressor status and/or signs of disease progression.</p

Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury

Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI

Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study

Background: In occupational settings, boilermakers are exposed to high levels of metallic fine particulate matter (PM2.5) generated during the welding process. The effect of welding PM2.5 on heart rate variability (HRV) has been described, but the relationship between PM2.5, DNA methylation, and HRV is not known. Methods: In this repeated-measures panel study, we recorded resting HRV and measured DNA methylation levels in transposable elements Alu and long interspersed nuclear element-1 (LINE-1) in peripheral blood leukocytes under ambient conditions (pre-shift) and right after a welding task (post-shift) among 66 welders. We also monitored personal PM2.5 level in the ambient environment and during the welding procedure. Results: The concentration of welding PM2.5 was significantly higher than background levels in the union hall (0.43 mg/m3 vs. 0.11 mg/m3, p < 0.0001). The natural log of transformed power in the high frequency range (ln HF) had a significantly negative association with PM2.5 exposure (β = -0.76, p = 0.035). pNN10 and pNN20 also had a negative association with PM2.5 exposure (β = -0.16%, p = 0.006 and β = -0.13%, p = 0.030, respectively). PM2.5 was positively associated with LINE-1 methylation [β = 0.79%, 5-methylcytosince (%mC), p = 0.013]; adjusted for covariates. LINE-1 methylation did not show an independent association with HRV. Conclusions: Acute decline of HRV was observed following exposure to welding PM2.5 and evidence for an epigenetic response of transposable elements to short-term exposure to high-level metal-rich particulates was reported. Electronic supplementary material The online version of this article (doi:10.1186/1471-2458-14-1279) contains supplementary material, which is available to authorized users

At-home blood collection and stabilization in high temperature climates using home RNA

Expanding whole blood sample collection for transcriptome analysis beyond traditional phlebotomy clinics will open new frontiers for remote immune research and telemedicine. Determining the stability of RNA in blood samples exposed to high ambient temperatures (\u3e30°C) is necessary for deploying home-sampling in settings with elevated temperatures (e.g., studying physiological response to natural disasters that occur in warm locations or in the summer). Recently, we have develope