The ELFIN mission

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E 1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.Published versio

Accelerating biopharma innovation through market discipline: an agent-based model of the pharmaceutical complex adaptive system

International audienc

Development of a quantitative fluorescence lateral flow immunoassay (LFIA) prototype for point-of-need detection of anti-Müllerian hormone

Objective: Anti-Müllerian Hormone (AMH) is a quantitative marker for ovarian reserve and is used to predict response during ovarian stimulation. Streamlining testing to the clinic or even to the physician's office would reduce inconvenience, turnaround time, patient stress and potentially also the total cost of testing, allowing for more frequent monitoring. In this paper, AMH is used as a model biomarker to describe the rational development and optimization of sensitive, quantitative, clinic-based rapid diagnostic tests. Design and Methods: We developed a one-step lateral-flow europium (III) chelate-based fluorescent immunoassay (LFIA) for the detection of AMH on a portable fluorescent reader, optimizing the capture/detection antibodies, running buffer, and reporter conjugates. Results: A panel of commercial calibrators was used to develop a standard curve to determine the analytical sensitivity (LOD = 0.41 ng/ml) and the analytical range (0.41–15.6 ng/ml) of the LFIA. Commercial controls were then tested to perform an initial evaluation of the prototype performance and showed a high degree of precision (Control I CV 2.18%; Control II CV 3.61%) and accuracy (Control I recovery 126%; Control II recovery 103%). Conclusions: This initial evaluation suggests that, in future clinical testing, the AMH LFIA will likely have the capability of distinguishing women with low ovarian reserve (6 ng/ml)

Lobular neoplasia at percutaneous breast biopsy: Variables associated with carcinoma at surgical excision

OBJECTIVE. The purpose of our study was to better define the rate and variables associated with cancer underestimation when lobular neoplasia is found at minimally invasive breast biopsy. MATERIALS AND METHODS. The records of 32,420 patients who underwent imaging-guided needle biopsy of the breast for mammographic or sonographic abnormalities from 1988 to 2000 were retrospectively reviewed. The 278 cases in which lobular neoplasia was the highest-risk lesion at biopsy were included. Of the 278 cases, 164 proceeded to surgical excision, allowing calculation of rates of underestimation from minimally invasive biopsy. RESULTS. Of the 32,420 minimally invasive breast biopsies, lobular neoplasia was found in 278 (0.9%). One hundred sixty-four of the 278 (59%) continued to surgical excision, where cancer was pathologically confirmed in 38 (23%). No difference was seen in the underestimation rates for lesions diagnosed as lobular carcinoma in situ (25%, 17 of 67 lesions) versus atypical lobular hyperplasia (22%, 21 of 97 lesions). Statistically significant underestimation of carcinoma was found with biopsy of masses (with or without associated microcalcifications) rather than calcifications only, a higher BI-RADS category (p \u3c 0.0001), use of a core biopsy device rather than a vacuum device (p \u3c 0.01), and obtaining fewer specimens (p \u3c 0.0001). CONCLUSION. Significant sampling error occurs regardless of the type of core biopsy device, number of specimens obtained, histologic-radiographic concordance, mammographic appearance, and complete excision of the lesion as determined by imaging. For this reason, all patients with lobular neoplasia at core or vacuum-assisted biopsy should undergo surgical excision until further differentiating criteria can be determined. © American Roentgen Ray Society

Expression and Characterization of Intein-Cyclized Trimer of <i>Staphylococcus aureus</i> Protein A Domain Z

Staphylococcus aureus protein A (SpA) is an IgG Fc-binding virulence factor that is widely used in antibody purification and as a scaffold to develop affinity molecules. A cyclized SpA Z domain could offer exopeptidase resistance, reduced chromatographic ligand leaching after single-site endopeptidase cleavage, and enhanced IgG binding properties by preorganization, potentially reducing conformational entropy loss upon binding. In this work, a Z domain trimer (Z3) was cyclized using protein intein splicing. Interactions of cyclic and linear Z3 with human IgG1 were characterized by differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC). DSF showed a 5 ℃ increase in IgG1 melting temperature when bound by each Z3 variant. SPR showed the dissociation constants of linear and cyclized Z3 with IgG1 to be 2.9 nM and 3.3 nM, respectively. ITC gave association enthalpies for linear and cyclic Z3 with IgG1 of −33.0 kcal/mol and −32.7 kcal/mol, and −T∆S of association 21.2 kcal/mol and 21.6 kcal/mol, respectively. The compact cyclic Z3 protein contains 2 functional binding sites and exhibits carboxypeptidase Y-resistance. The results suggest cyclization as a potential approach toward more stable SpA-based affinity ligands, and this analysis may advance our understanding of protein engineering for ligand and drug development